Design And Synthesis Of Quinazoline EGFR Inhibitors

Since the 21 st centry,along with the rapid development of bioscience,the genetical mechanism of birth and development of tumor have been gradualy realized by molecular biologists.The research of antitumor drugs has entered a new stage of targeted drug synthesis.As a banch of drugs based on tumor signal transduction mechanism,protein kinase inhibitors have attracted a wide spread attention,among which quinazoline as one of highly active and selective epidermal growth factor receptor(EGFR)inhibitors has been one of the hot research spot.In this study,based on the review of literatures at home and abroad,the research purpose,meanings and plan were first presented,then the molecular structures with high score were obtained through computer simulation,and finally the synthesis and structure characterization about these compounds were carried out to lay a good foundation for future study.In the first section,the world wide development of antineoplastic drugs is stated.All kinds of the activity of antineoplastic drugs and mechanism are firstly analyzed and compared,hence the importance of protein kinase inhibitors is emphasized.Then,the purpose and plan of this study are presented through analyzing the development of epidermal growth factor receptor(EGFR)inhibitors,and the synthetic methods of quinazoline derivatives,and also the present situation of computer simulation.In the second section,the application of Discovery Studio software was carried out to realize the rapid molecular docking and some quinazoline derivatives with high score were screened using LibDock art which thus laid a good foundation for next research.In the third section,using 2-aminobenzonitriles,aromatic amines and DMF as raw materials,the different synthetic methods especially routes and catalysts for quinazoline derivatives were investigated.The result of optimum experiment has a certain guiding significance for industrial production.In the fourth section,the simulated structures were synthesized with 2-aminobenzonitriles,formamide and carboxylic acids,and their synthesis process was discussed.The targeted compounds which their quinazoline skeleton linked with naproxen,ibuprofen,styrene acrylic acid by amide bond,were obtained and characterized with 1H-NMR,IR and ESI-MS methods.AnaaThis research shows that using computer simulation software to get the molecular structure with potential pharmacological activity,has the advantages of time-saving,intuitive and efficient,thus is important in guiding drug design.Through discussing different synthetic methods to discover the nature of reaction,has a important role in guiding drug research.